DESCRIPTION: (Applicant's Abstract) The applicant proposes to accomplish a phase II study of the novel anticancer agent Bryostatin 1 in metastatic melanoma and use laboratory investigations to evaluate the biochemistry, mechanism of action and pharmacology of this agent. Bryostatin I is a macrocyclic lactone isolated from a marine Bryozoan which functions by activating protein kinase C. He and others have demonstrated that it inhibits the growth of melanoma in animals. These results led to phase I testing of Bryostatin 1 in humans which defined a dose and schedule for the administration of Bryostatin 1 and demonstrated that Bryostatin 1 had a limited set of side effects. In phase I testing two patients with metastatic melanoma had a partial response to this agent. The aims of this phase II trial are: (1) to carry out a phase II study of bryostatin 1 and evaluate the percentage of patients with metastatic melanoma responding to this agent; (2) to determine whether bryostatin 1 induces apoptosis in tumor samples: (3) to examine whether tumor responses correlate with the regulation of protein kinase C or gene induction; (4) to determine whether bryostatin 1 activates lymphocytes to kill tumor tissues; and (5) to accomplish Bryostatin 1 pharmacology using a novel assay. For this pilot study the applicant proposes to treat 14 patients using an established phase I regimen once a week every three out of four weeks at a dose of 25 ug/m2 infused over one hour. If a response is seen in the first 14 patients, a total of 25 patients will be treated. Patients who have not received any chemo- or immunotherapy and have easily biopsied lesions will be eligible. Biopsies of melanoma lesions will be done before and after therapy to assess biomarkers and intermediate end points. Blood will be drawn before, during and after infusion and examined for platelet and neutrophil activation, protein kinase levels and changes in gene transcription. As long as a partial or complete response is evident, treatment will be continued.